Antioksidansi za smanjenu plodnost žena
Appendices
Appendix 1. Cochrane Gynaecology and Fertility specialised register search strategy
PROCITE platform
Searched 12 September 2019
Keywords CONTAINS "antioxidants"or "antioxidant" or "antioxidant levels" or "vitamin" or "vitamin A" or "vitamin B" or "Vitamin‐B‐12" or "Vitamin‐B‐12‐Therapeutic‐Use" or "vitamin B6" or "vitamin C" or "Vitamin D" or "vitamin E" or "vitamins" or "selenium" or "folic acid" or "glutathione" or "Menevit anti‐oxidant" or "carnitene" or "carnitine" or "ascorbic acid" or "zinc" or "fatty acids" or "oil" or "fish oils" or "plant extracts" or "tocopherol"or"ubiquinol "or"coenzyme Q10"or "multivitamins"or "N‐acetyl cysteine"or "L‐acetyl‐carnitine"or"acetyl L‐carnitine"or "acetylcysteine"or"alpha tocopherol"or"pycnogenol"or"Myo‐inositol"or "inositol"or "melatonin" or Title CONTAINS "antioxidants" or "antioxidant"or"antioxidant levels" or "vitamin" or "vitamin A" or "vitamin B" or "Vitamin‐B‐12" or "Vitamin‐B‐12‐Therapeutic‐Use" or "vitamin B6" or "vitamin C" or "Vitamin D" or "vitamin E" or "vitamins" or "selenium" or "folic acid" or "glutathione" or "Menevit anti‐oxidant" or "carnitene" or "carnitine" or "ascorbic acid" or "zinc"or "Myo‐inositol"or "inositol"or "melatonin"
AND
Keywords CONTAINS "IVF" or "ICSI" or "in‐vitro fertilisation " or "in‐vitro fertilisation procedure" or "in vitro fertilization" or "intracytoplasmic sperm injection" or "intracytoplasmic morphologically selected sperm injection" or "superovulation" or "superovulation induction" or "IUI" or "insemination, intrauterine " or "Intrauterine Insemination" or "ART" or "artificial insemination" or "assisted reproduction techniques" or "subfertility‐Female" or "Polycystic Ovary Syndrome" or "PCOS" or "endometriosis"or "subfertility" or "unexplained and endometriosis related infertility" or"unexplained infertility" or"unexplained subfertility" or Title CONTAINS"IVF" or "ICSI" or "in‐vitro fertilisation " or "in‐vitro fertilisation procedure" or "in vitro fertilization" or "intracytoplasmic sperm injection" or "intracytoplasmic morphologically selected sperm injection" or "superovulation" or "superovulation induction" or "IUI" or "insemination, intrauterine " or "Polycystic Ovary Syndrome" or "subfertility"
(529 records)
Appendix 2. Cochrane CENTRAL Register of Studies Online (CRSO)
Web platform
Searched 12 September 2019
#1 MESH DESCRIPTOR Antioxidants EXPLODE ALL TREES 14668
#2 MESH DESCRIPTOR free radical scavengers EXPLODE ALL TREES 4969
#3 (antioxidant* or radical scavenger*):TI,AB,KY 11407
#4 MESH DESCRIPTOR Vitamins EXPLODE ALL TREES 17099
#5 MESH DESCRIPTOR Ascorbic Acid EXPLODE ALL TREES 2104
#6 vitamin*:TI,AB,KY 27018
#7 (zinc or selenium):TI,AB,KY 8015
#8 (Glutathione* or folate):TI,AB,KY 5278
#9 (ubiquin* or folic acid):TI,AB,KY 4764
#10 (coenzyme q10):TI,AB,KY 795
#11 MESH DESCRIPTOR Acetylcarnitine EXPLODE ALL TREES 119
#12 MESH DESCRIPTOR Carnitine EXPLODE ALL TREES 586
#13 (carnitine* or carotenoid):TI,AB,KY 2146
#14 (astaxanthin* or lycopene):TI,AB,KY 736
#15 multivitamin*:TI,AB,KY 1083
#16 (ascorbic acid):TI,AB,KY 3505
#17 n‐acetylcysteine:TI,AB,KY 1464
#18 MESH DESCRIPTOR Acetylcysteine EXPLODE ALL TREES 959
#19 MESH DESCRIPTOR alpha‐Tocopherol EXPLODE ALL TREES 546
#20 alpha‐tocopherol:TI,AB,KY 2320
#21 (fish adj2 oil*):TI,AB,KY 2718
#22 omega:TI,AB,KY 5664
#23 MESH DESCRIPTOR Fish Oils EXPLODE ALL TREES 3136
#24 (fatty acid*):TI,AB,KY 15640
#25 l‐arginine:TI,AB,KY 1345
#26 (n acetyl cysteine):TI,AB,KY 372
#27 melatonin:TI,AB,KY 2372
#28 (dietary supplement*):TI,AB,KY 12103
#29 MESH DESCRIPTOR Dietary Supplements EXPLODE ALL TREES 11121
#30 (nutritional supplement*):TI,AB,KY 2241
#31 micronutrient*:TI,AB,KY 2343
#32 Nutraceutical*:TI,AB,KY 507
#33 (myoinositol or mesoinositol or Inositol):TI,AB,KY 706
#34 MESH DESCRIPTOR Inositol EXPLODE ALL TREES 413
#35 MESH DESCRIPTOR Pentoxifylline EXPLODE ALL TREES 535
#36 Pentoxifylline:TI,AB,KY 1133
#37 #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31 OR #32 OR #33 OR #34 OR #35 OR #36 85690
#38 MESH DESCRIPTOR Embryo Transfer EXPLODE ALL TREES 1058
#39 MESH DESCRIPTOR Fertilization in Vitro EXPLODE ALL TREES 1997
#40 MESH DESCRIPTOR Sperm Injections, Intracytoplasmic EXPLODE ALL TREES 525
#41 (embryo* adj2 transfer*):TI,AB,KY 3717
#42 (vitro fertili?ation):TI,AB,KY 3231
#43 ivf:TI,AB,KY 5281
#44 icsi:TI,AB,KY 2536
#45 (intracytoplasmic sperm injection*):TI,AB,KY 1833
#46 (blastocyst* adj2 transfer*):TI,AB,KY 379
#47 MESH DESCRIPTOR Reproductive Techniques, Assisted EXPLODE ALL TREES 3062
#48 (assisted reproduct*):TI,AB,KY 1349
#49 (artificial insemination):TI,AB,KY 242
#50 MESH DESCRIPTOR Insemination, Artificial EXPLODE ALL TREES 358
#51 IUI:TI,AB,KY 839
#52 (intrauterine insemination*):TI,AB,KY 952
#53 (ovulation induc*):TI,AB,KY 2494
#54 (ovar* adj2 stimulat*):TI,AB,KY 2106
#55 superovulat*:TI,AB,KY 213
#56 (ovarian hyperstimulation):TI,AB,KY 1345
#57 COH:TI,AB,KY 385
#58 infertil*:TI,AB,KY 7867
#59 subfertil*:TI,AB,KY 888
#60 (ovar* adj2 induction):TI,AB,KY 231
#61 #38 OR #39 OR #40 OR #41 OR #42 OR #43 OR #44 OR #45 OR #46 OR #47 OR #48 OR #49 OR #50 OR #51 OR #52 OR #53 OR #54 OR #55 OR #56 OR #57 OR #58 OR #59 OR #60 14082
#62 #37 AND #61 798
Appendix 3. MEDLINE search strategy
OVID platform
Searched from 1946 to 12 September 2019
1 exp antioxidants/ or free radical scavengers/ (450779)
2 (antioxidant$ or radical scavengers).tw. (187413)
3 exp vitamins/ or exp ascorbic acid/ or exp dehydroascorbic acid/ or exp vitamin a/ or exp vitamin e/ or exp vitamin u/ or exp alpha‐tocopherol/ or exp beta carotene/ or exp beta‐tocopherol/ or exp gamma‐tocopherol/ (333915)
4 vitamin$.tw. (199584)
5 exp Zinc/ (58586)
6 (zinc or selenium).tw. (133593)
7 exp Selenium/ (20073)
8 exp Glutathione Peroxidase/ or exp folic acid/ (55638)
9 (Glutathione$ or folate).tw. (145559)
10 exp Ubiquinone/ (8918)
11 (ubiquin$ or folic acid).tw. (27862)
12 coenzyme q10.tw. (3284)
13 exp Carnitine/ (9416)
14 (carnitine$ or carotenoid$).tw. (33590)
15 (astaxanthin$ or lycopene$).tw. (6542)
16 multivitamin$.tw. (3648)
17 (betacarotene$ or beta carotene$).tw. (13423)
18 ascorbic acid.tw. (30335)
19 n‐acetylcysteine.tw. (10906)
20 exp Acetylcysteine/ (12772)
21 alpha‐tocopherol$.tw. (15310)
22 (fish adj2 oil$).tw. (10343)
23 omega$.tw. (49466)
24 exp fatty acids/ or exp fish oils/ or exp cod liver oil/ or exp fatty acids, omega‐3/ or exp plant oils/ (472246)
25 fatty acid$.tw. (203789)
26 (plant adj4 oil$).tw. (2856)
27 l‐arginine$.tw. (33412)
28 (flavonoid$ or Quercetin).tw. (48080)
29 exp Flavonoids/ (107908)
30 riboflavin$.tw. (9909)
31 pycnogenol$.tw. (384)
32 lutein$.tw. (37948)
33 lipoic acid$.tw. (4356)
34 n acetyl cysteine.tw. (3417)
35 melatonin.tw. (23152)
36 dietary supplement$.tw. (17596)
37 nutritional supplement$.tw. (5939)
38 micronutrient$.tw. (14121)
39 Nutraceuticals$.tw. (2640)
40 exp Chromium/ or chromium.tw. or chromax.tw. (34790)
41 (myoinositol or mesoinositol or Inositol).tw. (36790)
42 exp Inositol/ (22811)
43 exp Pentoxifylline/ or Pentoxifylline$.tw. (5203)
44 or/1‐43 (1789053)
45 exp Infertility, Female/ (27850)
46 female$ subfertil$.tw. (83)
47 female$ infertilit$.tw. (1599)
48 (subfertil$ adj5 women).tw. (585)
49 (infertil$ adj5 women).tw. (8464)
50 female$ fertility.tw. (2144)
51 (in vitro fertilisation or intracytoplasmic sperm injection$).tw. (8444)
52 intrauterine insemination$.tw. (2418)
53 (ivf or icsi or iui).tw. (27383)
54 in vitro fertilization.tw. (20500)
55 ART.tw. (93602)
56 Assisted reproducti$.tw. (14069)
57 ovulation induction.tw. (3491)
58 ovarian hyperstimulation.tw. (4914)
59 or/45‐58 (165914)
60 randomized controlled trial.pt. (489083)
61 controlled clinical trial.pt. (93275)
62 randomized.ab. (454403)
63 placebo.tw. (206202)
64 clinical trials as topic.sh. (188281)
65 randomly.ab. (318000)
66 trial.ti. (204626)
67 (crossover or cross‐over or cross over).tw. (81635)
68 or/60‐67 (1267341)
69 (animals not (humans and animals)).sh. (4584154)
70 68 not 69 (1164369)
71 44 and 59 and 70 (865)
Appendix 4. Embase search strategy
OVID platform
Searched from 1980 to 12 September 2019
1 exp antioxidants/ or free radical scavengers/ (201452)
2 (antioxidant$ or radical scavengers).tw. (244217)
3 vitamin$.tw. (237423)
4 exp vitamin/ or exp ascorbic acid/ or exp carotenoid/ or exp tocopherol/ (573159)
5 exp Zinc/ (100860)
6 (zinc or selenium).tw. (147362)
7 exp Selenium/ (35153)
8 exp chromium picolinate/ or Chromium.tw. or chromax.tw. (25942)
9 exp Glutathione Peroxidase/ or exp folic acid/ (93347)
10 (Glutathione$ or folate).tw. (168513)
11 exp Ubiquinone/ (7145)
12 (ubiquin$ or folic acid).tw. (31265)
13 coenzyme q10.tw. (4641)
14 exp Carnitine/ (14458)
15 (carnitine$ or carotenoid$).tw. (37897)
16 (astaxanthin$ or lycopene$).tw. (7735)
17 multivitamin$.tw. (4983)
18 (betacarotene$ or beta carotene$).tw. (15246)
19 ascorbic acid.tw. (31529)
20 n‐acetylcysteine.tw. (14087)
21 exp acetylcysteine/ (34238)
22 n‐acetyl‐cysteine.tw. (4679)
23 alpha‐tocopherol$.tw. (16240)
24 (fish adj2 oil$).tw. (13130)
25 omega$.tw. (50193)
26 fatty acid$.tw. (226006)
27 exp edible oil/ or exp castor oil/ or exp cod liver oil/ or exp fish oil/ or exp lyprinol/ or exp olive oil/ or exp safflower oil/ or exp fatty acid/ or exp essential fatty acid/ or exp arachidonic acid/ or exp linoleic acid/ or exp linolenic acid/ or exp gamma linolenic acid/ or exp unsaturated fatty acid/ or exp omega 3 fatty acid/ or exp omega 6 fatty acid/ or exp polyunsaturated fatty acid/ (553010)
28 (plant adj4 oil$).tw. (3955)
29 l‐arginine$.tw. (37405)
30 (flavonoid$ or Quercetin).tw. (67755)
31 riboflavin$.tw. (9540)
32 pycnogenol$.tw. (491)
33 lipoic acid$.tw. (5383)
34 melatonin.tw. (28312)
35 dietary supplement$.tw. (21900)
36 micronutrient$.tw. (18636)
37 nutritional supplement$.tw. (8229)
38 Nutraceutical$.tw. (7566)
39 exp inositol/ (10942)
40 (Inositol or mesoinositol or myoinositol).tw. (39887)
41 exp Pentoxifylline/ or Pentoxifylline$.tw. (13513)
42 or/1‐41 (1914706)
43 exp Infertility, Female/ (41066)
44 (female$ adj2 subfertil$).tw. (219)
45 (female$ adj2 infertilit$).tw. (2861)
46 (subfertil$ adj2 women).tw. (741)
47 (infertil$ adj2 women).tw. (9098)
48 (female$ adj2 fertility).tw. (3341)
49 (vitro fertilisation or intracytoplasmic sperm injection$).tw. (11556)
50 (intrauterine adj3 insemination$).tw. (3737)
51 (ivf or icsi or iui).tw. (47478)
52 vitro fertilization.tw. (26672)
53 Artificial reproduc$ technique$.tw. (204)
54 Assisted reproducti$.tw. (21695)
55 exp artificial insemination/ or exp fertilization in vitro/ or exp intracytoplasmic sperm injection/ or exp intrauterine insemination/ (77680)
56 exp Superovulation/ (2788)
57 Superovulation.tw. (2305)
58 or/43‐57 (144258)
59 Clinical Trial/ (952533)
60 Randomized Controlled Trial/ (565068)
61 exp randomization/ (84159)
62 Single Blind Procedure/ (36462)
63 Double Blind Procedure/ (162252)
64 Crossover Procedure/ (60492)
65 Placebo/ (327459)
66 Randomi?ed controlled trial$.tw. (210783)
67 Rct.tw. (33803)
68 random allocation.tw. (1909)
69 randomly allocated.tw. (33204)
70 allocated randomly.tw. (2474)
71 (allocated adj2 random).tw. (809)
72 Single blind$.tw. (23300)
73 Double blind$.tw. (195064)
74 ((treble or triple) adj blind$).tw. (1005)
75 placebo$.tw. (290276)
76 prospective study/ (548416)
77 or/59‐76 (2077888)
78 case study/ (64016)
79 case report.tw. (380889)
80 abstract report/ or letter/ (1072000)
81 or/78‐80 (1507016)
82 77 not 81 (2026320)
83 42 and 58 and 82 (1562)
Appendix 5. PsycINFO search strategy
OVID platform
Searched from 1806 to 12 September 2019
1 exp Antioxidants/ (2646)
2 (antioxidant$ or radical scavengers).tw. (5404)
3 exp Vitamins/ (4662)
4 vitamin$.tw. (7099)
5 exp Zinc/ (816)
6 (zinc or selenium).tw. (2421)
7 (Glutathione$ or folate).tw. (3760)
8 (ubiquin$ or folic acid).tw. (870)
9 (coenzyme q10 or chromium).tw. (328)
10 (carnitine$ or carotenoid$).tw. (791)
11 multivitamin$.tw. (241)
12 (betacarotene$ or beta carotene$).tw. (146)
13 ascorbic acid.tw. (428)
14 n‐acetylcysteine.tw. (417)
15 alpha‐tocopherol$.tw. (226)
16 (fish adj2 oil$).tw. (307)
17 omega$.tw. (2730)
18 exp Fatty Acids/ (4830)
19 fatty acid$.tw. (4449)
20 l‐arginine$.tw. (1109)
21 melatonin.tw. (4582)
22 dietary supplement$.tw. (991)
23 nutritional supplement$.tw. (579)
24 micronutrient$.tw. (626)
25 Nutraceuticals$.tw. (107)
26 (Pentoxifylline or myoinositol or inositol).tw. (1693)
27 or/1‐26 (34273)
28 exp Infertility/ (2093)
29 (female$ adj2 subfertil$).tw. (2)
30 (female$ adj2 infertil$).tw. (210)
31 (subfertil$ adj2 women).tw. (8)
32 (infertil$ adj2 women).tw. (464)
33 female$ fertility.tw. (151)
34 (vitro fertilisation or intracytoplasmic sperm injection$).tw. (165)
35 intrauterine insemination$.tw. (27)
36 (ivf or icsi or iui).tw. (604)
37 vitro fertilization.tw. (654)
38 Artificial reproduc$ technique$.tw. (15)
39 Assisted reproducti$.tw. (925)
40 or/28‐39 (3533)
41 27 and 40 (31)
Appendix 6. AMED search strategy
OVID platform
Searched from 1985 to 12 September 2019
1 exp Antioxidants/ or exp Free radicals/ (2511)
2 (antioxidant$ or radical scavengers).tw. (3507)
3 exp Vitamins/ or exp Dietary supplements/ (4384)
4 exp Ascorbic acid/ (308)
5 vitamin$.tw. (2623)
6 exp Zinc/ (126)
7 (zinc or selenium).tw. (505)
8 (Glutathione$ or folate).tw. (877)
9 exp Selenium/ (106)
10 (ubiquin$ or folic acid).tw. (190)
11 coenzyme q10.tw. (88)
12 exp Carnitine/ (20)
13 chromium.tw. (91)
14 (carnitine$ or carotenoid$).tw. (237)
15 multivitamin$.tw. (70)
16 ascorbic acid.tw. (519)
17 n‐acetylcysteine.tw. (35)
18 Acetylcysteine.tw. (37)
19 alpha‐tocopherol$.tw. (91)
20 (fish adj2 oil$).tw. (193)
21 omega$.tw. (280)
22 exp Fatty acids/ (651)
23 exp Fish oils/ (118)
24 fatty acid$.tw. (977)
25 (plant adj4 oil$).tw. (1089)
26 l‐arginine$.tw. (142)
27 (flavonoid$ or Quercetin).tw. (1920)
28 riboflavin$.tw. (24)
29 pycnogenol$.tw. (18)
30 micronutrient$.tw. (126)
31 nutriceutical$.tw. (10)
32 dietary supplement$.tw. (1841)
33 Pentoxifylline$.tw. (12)
34 (myoinositol or inositol).tw. (58)
35 melatonin.tw. (119)
36 or/1‐35 (11918)
37 exp Infertility female/ (203)
38 (female$ adj3 subfertil$).tw. (0)
39 (female$ adj3 infertil$).tw. (211)
40 (subfertil$ adj3 women).tw. (2)
41 (infertil$ adj3 women).tw. (41)
42 female$ fertility.tw. (8)
43 (vitro fertilisation or intracytoplasmic sperm injection$).tw. (24)
44 intrauterine insemination$.tw. (7)
45 (ivf or icsi or iui).tw. (50)
46 in vitro fertilization.tw. (28)
47 assisted reproduct$ techn$.tw. (23)
48 or/37‐47 (264)
49 36 and 48 (5)
Appendix 7. CINAHL search strategy
EBSCO platform
Searched from 1961 to 12 September 2019
S63 S50 AND S62 96
S62 S51 OR S52 OR S53 OR S54 OR S55 OR S56 OR S57 OR S58 OR S59 OR S60 OR S61 1,348,929
S61 TX allocat* random* 10,957
S60 (MH "Quantitative Studies") 23,242
S59 (MH "Placebos") 11,447
S58 TX placebo* 58,990
S57 TX random* allocat* 10,957
S56 (MH "Random Assignment") 56,426
S55 TX randomi* control* trial* 174,871
S54 TX ( (singl* n1 blind*) or (singl* n1 mask*) ) or TX ( (doubl* n1 blind*) or (doubl* n1 mask*) ) or TX ( (tripl* n1 blind*) or (tripl* n1 mask*) ) or TX ( (trebl* n1 blind*) or (trebl* n1 mask*) ) 1,031,287
S53 TX clinic* n1 trial* 250,249
S52 PT Clinical trial 86,854
S51 (MH "Clinical Trials+") 266,333
S50 S26 AND S49 375
S49 S27 OR S28 OR S29 OR S30 OR S31 OR S32 OR S33 OR S34 OR S35 OR S36 OR S37 OR S38 OR S39 OR S40 OR S41 OR S42 OR S43 OR S44 OR S45 OR S46 OR S47 OR S48 15,649
S48 TX intra‐uterine insemination 29
S47 TX natural cycle* 363
S46 TX timed intercourse 38
S45 TX (ovari* N2 induction) 34
S44 TX COH 232
S43 TX ovarian hyperstimulation 808
S42 TX superovulat* 82
S41 TX ovulation induc* 1,720
S40 TX intrauterine insemination 461
S39 TX IUI 335
S38 TX artificial insemination 769
S37 TX assisted reproduct* 3,692
S36 (MM "Insemination, Artificial") 428
S35 (MM "Reproduction Techniques+") 8,754
S34 TX intracytoplasmic sperm injection* 864
S33 TX embryo* N3 transfer* 2,981
S32 TX ovar* N3 hyperstimulat* 813
S31 TX ovari* N3 stimulat* 968
S30 TX IVF or TX ICSI 4,829
S29 (MM "Fertilization in Vitro") 3,357
S28 TX vitro fertilization 6,786
S27 TX vitro fertilisation 6,786
S26 S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR S18 OR S19 OR S20 OR S21 OR S22 OR S23 OR S24 OR S25 160,786
S25 TX Nutraceutical* 1,625
S24 TX micronutrient* 6,074
S23 TX nutritional supplement* 2,855
S22 TX dietary supplement* 39,500
S21 TX melatonin 3,042
S20 TX n acetyl cysteine 472
S19 TX l‐arginine 1,681
S18 TX (fish N2 oil*) 4,039
S17 (MH "Acetylcysteine") 1,450
S16 TX n‐acetylcysteine 1,204
S15 TX ascorbic acid 5,628
S14 TX multivitamin* 1,563
S13 TX(astaxanthin* or lycopene*) 1,286
S12 TX (carnitine* or carotenoid*) 4,485
S11 (MM "Carnitine") 665
S10 TX coenzyme q10 645
S9 TX (ubiquin* or folic acid) 8,278
S8 TX (zinc or selenium) 10,413
S7 TX omega$ 2,692
S6 TX fatty acid* 27,131
S5 (MH "Fatty Acids, Omega 3") OR (MH "Fatty Acids, Unsaturated+") 23,362
S4 TX vitamin* 53,224
S3 (MH "Vitamins+") 47,086
S2 TX antioxidant* 27,638
S1 (MM "Antioxidants+") 9,064
Appendix 8. Search strategies for The WHO portal (ICTRP), clinicaltrials.gov, Google, DARE, Web of Knowledge and OpenGrey
Web platforms
Searched 12 September 2019
'antioxidants and subfertility', 'antioxidants and infertility', 'vitamin and subfertility', 'vitamin and infertility', 'N‐acetyl‐cysteine and subfertility', 'N‐acetyl‐cysteine and infertility', 'myo‐inositol and subfertility', 'myo‐inositol and subfertility', 'fatty acids and subfertility' and 'fatty acids and infertility'
Methodological risk of bias summary: review authors' judgements about each methodological bias item for each included study.
Methodological risk of bias graph: review authors' judgements about each methodological bias item presented as percentages across all included trials.
Funnel plot of comparison: 1 Antioxidant(s) versus placebo or no treatment/standard treatment, outcome: 1.5 Clinical pregnancy; antioxidants vs placebo or no treatment/standard treatment (natural conceptions and undergoing fertility treatments).
Forest plot of comparison: 1 Antioxidant(s) versus placebo or no treatment/standard treatment, outcome: 1.1 Live birth; antioxidants vs placebo or no treatment/standard treatment (natural conceptions and undergoing fertility treatments).
Forest plot of comparison: 1 Antioxidant(s) versus placebo or no treatment/standard treatment, outcome: 1.5 Clinical pregnancy; antioxidants vs placebo or no treatment/standard treatment (natural conceptions and undergoing fertility treatments).
Forest plot of comparison: 1 Antioxidant(s) versus placebo or no treatment/standard treatment, outcome: 1.9 Adverse events.
Forest plot of comparison: 2 Head‐to‐head antioxidants, outcome: 2.1 Live birth; type of antioxidant (natural conceptions and undergoing fertility treatments).
Forest plot of comparison: 2 Head‐to‐head antioxidants, outcome: 2.4 Clinical pregnancy; type of antioxidant (natural conceptions and undergoing fertility treatments).
Forest plot of comparison: 2 Head‐to‐head antioxidants, outcome: 2.7 Adverse events.
Comparison 1: Antioxidant(s) versus placebo or no treatment/standard treatment, Outcome 1: Live birth; antioxidants vs placebo or no treatment/standard treatment (natural conceptions and undergoing fertility treatments)
Comparison 1: Antioxidant(s) versus placebo or no treatment/standard treatment, Outcome 2: Live birth; type of antioxidant
Comparison 1: Antioxidant(s) versus placebo or no treatment/standard treatment, Outcome 3: Live birth; indications for subfertility
Comparison 1: Antioxidant(s) versus placebo or no treatment/standard treatment, Outcome 4: Live birth; IVF/ICSI
Comparison 1: Antioxidant(s) versus placebo or no treatment/standard treatment, Outcome 5: Clinical pregnancy; antioxidants vs placebo or no treatment/standard treatment (natural conceptions and undergoing fertility treatments)
Comparison 1: Antioxidant(s) versus placebo or no treatment/standard treatment, Outcome 6: Clinical pregnancy; type of antioxidant
Comparison 1: Antioxidant(s) versus placebo or no treatment/standard treatment, Outcome 7: Clinical pregnancy; indications for subfertility
Comparison 1: Antioxidant(s) versus placebo or no treatment/standard treatment, Outcome 8: Clinical pregnancy; IVF/ICSI
Comparison 1: Antioxidant(s) versus placebo or no treatment/standard treatment, Outcome 9: Adverse events
Comparison 2: Head‐to‐head antioxidants, Outcome 1: Live birth; type of antioxidant (natural conceptions and undergoing fertility treatments)
Comparison 2: Head‐to‐head antioxidants, Outcome 2: Live Birth; indications for subfertility
Comparison 2: Head‐to‐head antioxidants, Outcome 3: Live Birth; IVF/ICSI
Comparison 2: Head‐to‐head antioxidants, Outcome 4: Clinical pregnancy; type of antioxidant (natural conceptions and undergoing fertility treatments)
Comparison 2: Head‐to‐head antioxidants, Outcome 5: Clinical pregnancy; indications for subfertility
Comparison 2: Head‐to‐head antioxidants, Outcome 6: Clinical pregnancy; IVF/ICSI
Comparison 2: Head‐to‐head antioxidants, Outcome 7: Adverse events
| Antioxidant(s) compared to placebo or no treatment/standard treatment for female subfertility | ||||||
| Patient or population: women with subfertility | ||||||
| Outcomes | Relative effect | Anticipated absolute effects* (95% CI) | Quality of the evidence | What happens | ||
|---|---|---|---|---|---|---|
| Without antioxidant(s) | With antioxidant(s) | Difference | ||||
| Live birth; antioxidants vs placebo or no treatment/standard treatment (natural conceptions and undergoing fertility treatments) | OR 1.81 | 19.0% | 29.8% | 10.8% more | ⊕⊝⊝⊝ | We are uncertain whether antioxidants improve live birth rate compared with placebo or no treatment/standard treatment. |
| Clinical pregnancy; antioxidants vs placebo or no treatment/standard treatment (natural conceptions and undergoing fertility treatments) | OR 1.65 | 18.8% | 27.6% | 8.8% more | ⊕⊕⊝⊝ | Antioxidant(s) may improve clinical pregnancy rate, compared with placebo or no treatment/standard treatment (natural conceptions and undergoing fertility treatments). |
| Adverse events ‐ Miscarriage | OR 1.13 | 4.8% | 5.4% | 0.6% more | ⊕⊕⊝⊝ | Antioxidant(s) may result in little to no difference in adverse events ‐ Miscarriage |
| Adverse events ‐ Multiple pregnancy | OR 1.00 | 4.3% | 4.3% | 0.0% fewer | ⊕⊕⊝⊝ | Antioxidant(s) may result in little to no difference in adverse events ‐ Multiple pregnancy |
| Adverse events ‐ Gastrointestinal disturbances | OR 1.55 | 2.4% | 3.7% | 1.3% more | ⊕⊕⊝⊝ | Antioxidant(s) may result in little to no difference in adverse events ‐ Gastrointestinal disturbances |
| Adverse events ‐ Ectopic pregnancy | OR 1.40 | 0.6% | 0.9% | 0.3% more | ⊕⊕⊝⊝ | Antioxidant(s) may result in little to no difference in adverse events ‐ Ectopic pregnancy |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| aDowngraded one level due to serious risk of bias. The no‐treatment group increases risk due to the lack of blinding. | ||||||
| Head‐to‐head antioxidants for female subfertility | ||||||
| Patient or population: women with subfertility | ||||||
| Outcomes | Relative effect | Anticipated absolute effects* (95% CI) | Quality of the evidence | What happens | ||
|---|---|---|---|---|---|---|
| With one antioxidant | With another antioxidant | Difference | ||||
| Live birth; type of antioxidant (natural conceptions and undergoing fertility treatments) ‐ Melatonin lower dose versus melatonin higher dose | OR 0.94 | 24.0% | 22.9% | 1.1% fewer | ⊕⊕⊝⊝ | There was no clear evidence of a difference between the lower and higher doses of melatonin |
| Clinical pregnancy; type of antioxidant (natural conceptions and undergoing fertility treatments) ‐ N‐acetylcysteine versus L‐carnitine | OR 0.81 | 14.6% | 12.2% | 2.4% fewer | ⊕⊝⊝⊝ | There was no clear evidence of a difference between N‐acetylcysteine versus L‐carnitine |
| Clinical pregnancy; type of antioxidant (natural conceptions and undergoing fertility treatments) ‐ Melatonin lower dose versus melatonin higher dose | OR 0.94 | 24.0% | 22.9% | 1.1% fewer | ⊕⊕⊝⊝ | There was no clear evidence of a difference between the lower and higher doses of melatonin |
| Adverse events ‐ Miscarriage | OR 1.54 (0.42 to 5.67) | 3.0% | 4.6% (1.3 to 15.1) | 1.6 more (1.7 fewer to 12.1 more) | ⊕⊕⊝⊝ | There were no miscarriages in either melatonin study (140 women) There was no clear evidence of a difference between N‐acetylcysteine versus L‐carnitine (164 women) |
| Adverse events ‐ Multiple pregnancy | There were no trials reporting multiple pregnancy | |||||
| Adverse events ‐ Gastrointestinal disturbances | There were no trials reporting gastrointestinal disturbances | |||||
| Adverse events ‐ Ectopic pregnancy Melatonin lower dose versus melatonin higher dose | Not estimable, there were no ectopic pregnancies in either group | ⊕⊝⊝⊝ | There was no clear evidence of a difference between the lower and higher doses of melatonin | |||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| aDowngraded one level as there are only two trials in this analysis and one is small. | ||||||
| Outcome | Data | Notes |
|---|---|---|
| Clinical pregnancy rate; myo‐inositol + folic acid | 4/23 | Only 42 of the 92 women enrolled in this trial declared a desire to become pregnant |
| Clinical pregnancy rate; folic acid + placebo | 1/19 | ‐ |
| Miscarriage rate; myo‐inositol + folic acid | Miscarriage reported, but unknown whether from treatment or control | 1 miscarriage occurred in the first trimester, but it is unknown from which group |
| Miscarriage rate; folic acid + placebo | Unknown | ‐ |
| Trial | Pregnancy in antioxidant group | Pregnancy in control group |
|---|---|---|
| 0/16 (vitamins C + E), at follow‐up over 9 months 3/16 | 0/18 (placebo), at follow‐up over 9 months 2/18 | |
| 9/22 (vitamin D) | 7/22 (placebo) | |
| 6/32 (selenium) | 1/32 (placebo) | |
| 20/60 (omega) | 15/58 (placebo) | |
| 7/33 (NAC + CC) | 5/33 (CC) | |
| 6/20 (selenium) | 5/20 (placebo) | |
| 5/20 (chromium) | 4/20 (placebo) | |
| 0/6 (myo‐inositol + 200 µg folic acid twice a day) | 0/6 (400 µg folic acid once a day) | |
| CC: clomiphene citrate; NAC: N‐acetylcysteine | ||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Live birth; antioxidants vs placebo or no treatment/standard treatment (natural conceptions and undergoing fertility treatments) Show forest plot | 13 | 1227 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.81 [1.36, 2.43] |
| 1.1.1 Placebo | 7 | 628 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.89 [1.18, 3.03] |
| 1.1.2 No treatment | 6 | 599 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.77 [1.22, 2.56] |
| 1.2 Live birth; type of antioxidant Show forest plot | 13 | 1227 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.81 [1.36, 2.43] |
| 1.2.1 N‐acetyl‐cysteine | 1 | 60 | Odds Ratio (M‐H, Fixed, 95% CI) | 3.00 [1.05, 8.60] |
| 1.2.2 L‐arginine | 1 | 37 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.43 [0.09, 2.09] |
| 1.2.3 CoQ10 | 2 | 225 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.50 [0.78, 2.88] |
| 1.2.4 Vitamin D | 1 | 52 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.79 [0.21, 3.02] |
| 1.2.5 Vitamin B complex | 1 | 102 | Odds Ratio (M‐H, Fixed, 95% CI) | 2.07 [0.93, 4.57] |
| 1.2.6 Combined antioxidants | 3 | 378 | Odds Ratio (M‐H, Fixed, 95% CI) | 2.59 [1.52, 4.40] |
| 1.2.7 Vitamin E | 1 | 103 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.43 [0.50, 4.10] |
| 1.2.8 Melatonin | 3 | 270 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.60 [0.68, 3.76] |
| 1.3 Live birth; indications for subfertility Show forest plot | 11 | Odds Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 1.3.1 Polycystic ovary syndrome | 3 | 362 | Odds Ratio (M‐H, Fixed, 95% CI) | 3.34 [1.90, 5.86] |
| 1.3.2 Tubal subfertility | 1 | 37 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.43 [0.09, 2.09] |
| 1.3.3 Varying indications | 3 | 338 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.70 [1.02, 2.83] |
| 1.3.4 Unexplained subfertility | 2 | 133 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.50 [0.60, 3.72] |
| 1.3.5 Poor ovarian reserve | 2 | 266 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.75 [0.83, 3.67] |
| 1.4 Live birth; IVF/ICSI Show forest plot | 9 | 806 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.36 [0.96, 1.93] |
| 1.5 Clinical pregnancy; antioxidants vs placebo or no treatment/standard treatment (natural conceptions and undergoing fertility treatments) Show forest plot | 35 | 5165 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.65 [1.43, 1.89] |
| 1.5.1 Placebo | 17 | 3292 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.70 [1.42, 2.05] |
| 1.5.2 No treatment/standard treatment | 19 | 1873 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.57 [1.28, 1.94] |
| 1.6 Clinical pregnancy; type of antioxidant Show forest plot | 35 | 5165 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.65 [1.43, 1.89] |
| 1.6.1 N‐acetylcysteine | 8 | 1590 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.36 [1.05, 1.77] |
| 1.6.2 Combined antioxidants | 5 | 689 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.90 [1.33, 2.70] |
| 1.6.3 Melatonin | 7 | 678 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.66 [1.12, 2.47] |
| 1.6.4 Vitamin E | 1 | 103 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.43 [0.50, 4.10] |
| 1.6.5 Ascorbic acid | 2 | 899 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.91 [0.66, 1.25] |
| 1.6.6 L‐arginine | 2 | 71 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.05 [0.32, 3.46] |
| 1.6.7 Myo‐inositol plus folic acid | 1 | 94 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.24 [0.50, 3.06] |
| 1.6.8 CoQ10 | 4 | 397 | Odds Ratio (M‐H, Fixed, 95% CI) | 2.49 [1.50, 4.13] |
| 1.6.9 L‐carnitine | 2 | 450 | Odds Ratio (M‐H, Fixed, 95% CI) | 11.14 [5.70, 21.81] |
| 1.6.10 Vitamin D | 2 | 92 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.83 [0.25, 2.76] |
| 1.6.11 Vitamin B complex | 1 | 102 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.94 [0.82, 4.58] |
| 1.7 Clinical pregnancy; indications for subfertility Show forest plot | 31 | Odds Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 1.7.1 Polycystic ovary syndrome | 15 | 1908 | Odds Ratio (M‐H, Fixed, 95% CI) | 4.24 [3.23, 5.56] |
| 1.7.2 Unexplained | 4 | 997 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.84 [0.61, 1.16] |
| 1.7.3 Tubal subfertility | 2 | 71 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.05 [0.32, 3.46] |
| 1.7.4 Varying indications | 6 | 1135 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.14 [0.85, 1.52] |
| 1.7.5 Poor responders | 1 | 65 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.88 [0.64, 5.47] |
| 1.7.6 Poor ovarian reserve | 2 | 266 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.70 [0.86, 3.37] |
| 1.7.7 Endometriosis | 1 | 280 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.19 [0.71, 1.98] |
| 1.8 Clinical pregnancy; IVF/ICSI Show forest plot | 18 | 2341 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.15 [0.95, 1.40] |
| 1.9 Adverse events Show forest plot | 27 | Odds Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 1.9.1 Miscarriage | 24 | 3229 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.13 [0.82, 1.55] |
| 1.9.2 Multiple pregnancy | 9 | 1886 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.00 [0.63, 1.56] |
| 1.9.3 Gastrointestinal disturbances | 3 | 343 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.55 [0.47, 5.10] |
| 1.9.4 Ectopic pregnancy | 4 | 404 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.40 [0.27, 7.20] |
| 1.9.5 Headache | 2 | 330 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.89 [0.45, 1.75] |
| 1.9.6 Congenital (missing kidney) | 1 | 160 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.02 [0.04, 25.46] |
| 1.9.7 Low birth weight < 2.500 g | 1 | 160 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.11 [0.00, 2.74] |
| 1.9.8 Preterm birth | 2 | 220 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.31 [0.17, 9.93] |
| 1.9.9 Placenta praevia | 1 | 160 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.02 [0.04, 25.46] |
| 1.9.10 Pre‐eclampsia | 1 | 160 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.71 [0.08, 36.35] |
| 1.9.11 Fatigue | 1 | 160 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.86 [0.75, 4.62] |
| 1.9.12 Ovarian hyperstimulation syndrome (OHSS) | 1 | 150 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 2.1 Live birth; type of antioxidant (natural conceptions and undergoing fertility treatments) Show forest plot | 2 | 140 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.94 [0.41, 2.15] |
| 2.1.1 Melatonin lower dose versus melatonin higher dose | 2 | 140 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.94 [0.41, 2.15] |
| 2.2 Live Birth; indications for subfertility Show forest plot | 2 | Odds Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 2.2.1 Unexplained subfertility | 1 | 20 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.00 [0.15, 6.77] |
| 2.2.2 Varying Indications | 1 | 120 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.93 [0.37, 2.32] |
| 2.3 Live Birth; IVF/ICSI Show forest plot | 2 | 140 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.94 [0.41, 2.15] |
| 2.4 Clinical pregnancy; type of antioxidant (natural conceptions and undergoing fertility treatments) Show forest plot | 3 | Odds Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 2.4.1 N‐acetylcysteine versus L‐carnitine | 1 | 164 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.81 [0.33, 2.00] |
| 2.4.2 Melatonin lower dose versus melatonin higher dose | 2 | 140 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.94 [0.41, 2.15] |
| 2.5 Clinical pregnancy; indications for subfertility Show forest plot | 3 | Odds Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 2.5.1 Polycystic ovary syndrome | 1 | 164 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.81 [0.33, 2.00] |
| 2.5.2 Unexplained subfertility | 1 | 20 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.00 [0.15, 6.77] |
| 2.5.3 Varying indications | 1 | 120 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.93 [0.37, 2.32] |
| 2.6 Clinical pregnancy; IVF/ICSI Show forest plot | 2 | 140 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.94 [0.41, 2.15] |
| 2.7 Adverse events Show forest plot | 3 | Odds Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 2.7.1 Miscarriage | 3 | 304 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.54 [0.42, 5.67] |
| 2.7.2 Ectopic pregnancy | 1 | 120 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 2.7.3 Congenital (missing kidney) | 1 | 120 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.53 [0.06, 38.36] |
| 2.7.4 Low birth weight < 2.500 g | 1 | 120 | Odds Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 2.7.5 Birth between 34 and 37 weeks | 1 | 120 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.49 [0.03, 8.10] |
| 2.7.6 Placenta praevia | 1 | 120 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.53 [0.06, 38.36] |
| 2.7.7 Pre‐eclampsia | 1 | 120 | Odds Ratio (M‐H, Fixed, 95% CI) | 0.49 [0.03, 8.10] |
